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Marie Linder,1 Anastasia Iliadou Nyman,2,3 Helle Kieler,1 Bengt Danielsson,2 Natalia Borg,2 Marcus Gry,2 Julius Collin2 1Centre for Pharmacoepidemiology, Karolinska Institutet, T2, Karolinska University Hospital, Stockholm, Sweden; 2The National Board of Health and Welfare, Stockholm, Sweden; 3Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, SwedenCorrespondence: Marie LinderCentre for Pharmacoepidemiology, Karolinska Institutet, T2, Karolinska University Hospital, Stockholm 171 76, SwedenTel +46 8-517 791 75Email marie.linder@ki.sePurpose: To evaluate associations between first-time use of direct oral anticoagulants or vitamin K antagonists and bleeding risk or mortality in the elderly with atrial fibrillation in a real-world setting in Sweden.Patients and Methods: The study population comprises first-time users, above age 60, of dabigatran, apixaban, rivaroxaban, or warfarin, with first atrial fibrillation occurrence within 6 months before dispensing (2012– 2016). Outcomes were gastrointestinal, any, or intracranial bleeding, and mortality. Exposure started at first dispensing of a study drug. Follow-up continued until outcome, end of drug supply, dispensing of another study drug, death or end of study (December 2016). We conducted a propensity score matched, nationwide register-based cohort study including three treatment groups: direct thrombin inhibitors, direct factor Xa inhibitors and vitamin K antagonists, each compared to the other two, focusing on subgroups of age and sex. Cox proportional hazard models adjusted for CHA2DS2VASc and HAS-BLED scores provided hazard ratios with 95% confidence intervals.Results: The matched study populations consisted of 7,264 patients for the direct thrombin inhibitors vs vitamin K antagonists comparison, 12,566 patients for the direct factor Xa inhibitors vs vitamin K antagonists comparison and 6,606 patients for the direct factor Xa inhibitors vs direct thrombin inhibitors comparison, in total 26,436 patients. Numerically high, but imprecise, hazard ratios for gastrointestinal bleeding were observed for women aged 75– 80, 80– 85, or above 85 years, eg 6.00 (1.02, 113.47) for direct thrombin inhibitors vs vitamin K antagonists. For both sexes, numerically high hazard ratios for any bleeding were observed in ages 80– 85, or above 85 years, eg 2.90 (1.01, 10.41) for direct thrombin inhibitors vs vitamin K antagonists. Numerically high HRs for intracranial bleeding were observed for women aged 75– 80 or 80– 85 years, eg 2.70 (0.65, 18.19) for direct factor Xa inhibitors vs vitamin K antagonists. Excess mortality was observed in both sexes, across age groups, for naive and experienced anticoagulant users.Conclusion: The observed increased gastrointestinal bleeding risk in first-time users of direct thrombin inhibitors or direct factor Xa inhibitors is consistent with previous studies. The possible risk of excess mortality merits further studies.Keywords: anticoagulants, arrhythmia, epidemiology, safety

Richard Thörn,1 Oskar Hemmingsson,2,3 Åsa Danielsson Borssén,1 Mårten Werner,1 Pontus Karling,1 Jonas Wixner1 1Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden; 2Department of Surgical and Perioperative Sciences, Umeå University, Umeå, Sweden; 3Wallenberg Centre for Molecular Medicine, Umeå University, Umeå, SwedenCorrespondence: Richard Thörn, Department of Public Health and Clinical Medicine, Faculty of Medicine, Umeå University, Umeå, S-901 87, Sweden, Tel +46706024820, Email richard.thorn@regionvasterbotten.sePurpose: Surveillance for hepatocellular carcinoma (HCC) is recommended in at-risk patients, but its effectiveness in Western populations has been questioned. The purpose was to evaluate the effect of surveillance in patients with HCC in a Northern European setting.Patients and Methods: Data on patients diagnosed with HCC between 2009 and 2019 were collected from the nationwide Swedish National Registry for Tumors of the Liver and Bile Ducts (SweLiv). Patients who had undergone HCC surveillance were compared to those who had not (but had an obvious indication for surveillance, ie, liver cirrhosis or hepatic porphyria and an age of ≥ 50 years) regarding etiology, tumor burden, presence of extrahepatic spread, treatment and lead-time adjusted overall survival.Results: A total of 4979 patients with index HCC were identified and information regarding surveillance was available in 4116 patients. Among these, 1078 had got their HCC diagnosis during surveillance, whereas 1647 had been diagnosed without surveillance despite a presumed indication. The most common underlying etiologies for HCC were hepatitis C (28.2%) and alcoholic liver disease (26.9%), and 94.8% had cirrhosis. The surveillance cohort more frequently met the University of California San Francisco-criteria (79% vs 53%, p < 0.001), more often received a potentially curative treatment (62% vs 28%, p < 0.001) and had less extrahepatic spread (7.6% vs 22.4% p < 0.001). After adjustment for lead-time bias (sojourn time of 270 days), the surveillance group had a significantly longer estimated median survival time than the non-surveillance group (34 months vs 11 months, p < 0.001). A multivariable cox regression analysis showed an adjusted hazard ratio of 0.59 (95% CI 0.51– 0.67) in favor of surveillance.Conclusion: Surveillance for HCC in at-risk patients is associated with diagnosis at an earlier tumor stage, treatment with curative intent and with improved lead-time adjusted overall survival. These findings encourage HCC surveillance of at-risk patients also in a Western population.Plain Language Summary: In this research article, we aimed to evaluate whether patients who have a known risk to develop liver cancer have a better prognosis if they undergo regular screening examinations with ultrasound every sixth months. Using information from a nationwide Swedish registry, we investigated the outcome in a large group of patients who had been diagnosed with liver cancer. We compared patients who had performed regular examinations to those who had not and concluded that the screening group had less advanced disease at diagnosis, as well as a better survival.Keywords: hepatocellular carcinoma, surveillance, survival, cirrhosis, chronic liver disease

Discusses the events that have led to the radioactive poisoning of the islands and inhabitants of French Polynesia as a result of French nuclear tests since 1966. Atmospheric testing under Gen. Charles de Gaulle; Fallout statistics; Opposition toatmospheric testing; Underground testing; Effects of storms and other accidents; Health problems; Verification problems. INSET: Cousteau out of his depth?, by B.D.; Tahiti secrets, by B.D.;L....